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Biomedical subjects

L J Harris

Publications and source records attributed to L J Harris.

At least 55 records · Page 3Linked to original sources

Emotional well-being among adolescents with and without chronic conditions.

PURPOSE: To investigate whether adolescents with chronic conditions differ from adolescents without chronic conditions in several psychological outcomes. An additional purpose was to explore whether adolescents with chronic conditions differ as a function of the visibility of their conditions. METHODS: By means of the Adolescent Health Survey, 1683 students (grades 7-12) with a variety of chronic conditions were compared with 1650 students without chronic conditions in regard to emotional well-being, worries and concerns, and body image. Differences in emotional well-being were examined as a function of perception of family connectedness. Comparisons were also made between adolescents with visible and invisible conditions. RESULTS: Adolescents with chronic conditions had lower emotional well-being scores, worried more about dying soon and about school or future work, and had poorer body image. For students with and without chronic conditions, higher emotional well-being scores were significantly related to higher levels of family connectedness. The best explanatory variables of emotional well-being were body image, family connectedness, concerns about school and future work, having a disability, and worry about peer relationships, accounting together for 36% of the variance in the outcome variable. No differences were found between adolescents with visible and invisible conditions. CONCLUSIONS: Although adolescents with chronic conditions do less well than adolescents without chronic conditions, having a disability is not the most influential factor on emotional well-being. Family connectedness is of fundamental importance for adolescents' emotional health.

Adolescent↗

Humanization of 60.3, an anti-CD18 antibody; importance of the L2 loop.

Monoclonal antibody 60.3 binds to the CD18 component of the beta 2 integrin family of adhesion molecules. 60.3 has potential clinical application in blocking the neutrophil-mediated organ damage which occurs following a myocardial infarct or hemorrhagic shock. Analysis of the nucleotide and deduced amino acid sequences of murine 60.3 shows that the light chain contains no amino acid substitutions relative to the closest germline sequence, while the heavy chain is heavily substituted. We report here the humanization of 60.3. The humanized antibody binds to CD18-bearing cells with approximately 4-fold less affinity than the murine or chimeric antibody. We have shown that modification of amino acid L50 in the L2 loop of the humanized antibody results in loss of binding, while modification of a structural determinant (H71) for the H2 loop has no effect.

Amino Acid Sequence↗

Methods to calculate the lens efficiency in optically coupled CCD x-ray imaging systems.

In lens-coupled CCD x-ray imaging, the lens efficiency is of critical importance for attaining an x-ray quantum-noise-limited system. However, the equations and the associated parameters of this process have not always been used properly in some of the literature. This can result in the incorrect estimation of the signal-to-noise ratio (SNR). In practice, it is found more convenient to use lens-coupling efficiency equations which assume that the scintillating screen is an extended Lambertian source, since the number of light photons emerging from various scintillating screens has been measured and reported by several investigators. This communication examines several of the most common types of lens-coupling efficiency equations and explains how to use them correctly with other parameters to calculate the SNR of a lens-coupled CCD x-ray imaging system.

Biophysical Phenomena↗

Neutrons confirmed in Nagasaki and at the Army Pulsed Radiation Facility: implications for Hiroshima.

Recent reports have clearly demonstrated that large discrepancies exist between neutron activation measured in Hiroshima and activation calculated using the current dosimetry system, DS86. The reports confirmed previous results for cobalt activation in Hiroshima that suggested problems, and this has spurred a joint U.S.-Japan effort to identify the source(s) of this discrepancy. Here, new results are presented that appear to eliminate both the measurements of neutron activation and the DS86 air-transport calculations as potential sources of the discrepancy in Hiroshima. Computer transport of DS86 fission neutrons through large distances of air was validated using concrete samples from Nagasaki and chloride detectors placed at selected distances from a bare uranium reactor. In both cases, accelerator mass spectrometry was used to measure thermal neutron activation via the reaction, 35Cl(n, gamma)36Cl (half-life, 301,000 years). Good agreement was observed between measurements of neutron activation and DS86 calculations for Nagasaki, as well as for the reactor experiment. Thus the large discrepancy observed in Hiroshima appears not to be due to uncertainties in air-transport calculations or in the activation measurements; rather, the discrepancy appears to be due to uncertainties associated with the Hiroshima bomb itself.

Chlorides↗

Vectors for the expression of PCR-amplified immunoglobulin variable domains with human constant regions.

Cassette vectors have been constructed for mammalian expression of complete immunoglobulin heavy and light chain genes whose variable regions are produced by the polymerase chain reaction (PCR). The light and heavy chain vectors have promoter, leader, partial intron, enhancer and constant region segments within modified pSV2-gpt and pSV2-neo plasmids, respectively. Variable (V) regions are obtained by PCR using a two step process: 1) the V gene is amplified from genomic or cDNA, cloned into an intermediate vector and sequenced; 2) the first PCR product serves as the template for a second amplification in which restriction enzyme recognition sites and limited flanking intron sequence are added. The second PCR product is inserted into the expression vector, which is then transfected into mouse myeloma cells. These vectors contain human constant regions and may be used to express chimeric, humanized or human Ig genes. This report describes the design of these vectors and their application for the expression of chimeric 60.3, an anti-CD18 antibody.

Animals↗

Effects of graded reductions in internal mammary artery bypass flow on left ventricular function.

This study investigated the controversial relationship between reduction in internal mammary artery (IMA) graft blood flow and left ventricular function in a canine model. Ten dogs underwent IMA grafting to the left anterior descending coronary artery. The left anterior descending coronary artery proximal to the IMA graft was intermittently occluded while IMA flow was mechanically controlled for 5-minute periods to produce four IMA flow groups representing 100%, 75%, 50%, and 25% of unoccluded IMA graft blood flow. As a control, the left ventricle was reperfused with native left anterior descending coronary artery flow between each IMA graft flow period to allow return to steady state. Sonomicrometry was used to obtain stroke work end-diastolic dimension relationship data for regional and global left ventricular function for each of the four flow groups. The global pressure recruitable work area relationship showed a significant rightward shift at 25% of unoccluded IMA flow, whereas the regional pressure recruitable work area relationship shifted at 50% of unoccluded IMA flow. Thus, regional myocardial function is more sensitive to reductions in IMA blood flow than is global left ventricular performance, and there is a significant IMA flow reserve for global left ventricular function.

Animals↗

Handedness, sex, and familial sinistrality effects on spatial tasks.

Left-handed (N = 109) and right-handed (N = 115) undergraduates (99 males, 125 females) received the SIBT (a "mental rotation" test), the 3DD (3-dimensional drawing test), and a family sinistrality (FS) questionnaire. Left-handers were further separated into consistent left-handed (CLH) and inconsistent left-handed (ILH) subgroups, based on consistency of hand preference. On the spatial tests, males outperformed females, with no overall handedness effects. Also, for males, CLH's (but not ILH's) performed significantly worse than right-handers on the SIBT, but this difference was not found on the 3DD. For females, no handedness subgroup differences were found on either spatial tasks. Familial sinistrality was twice as common in left-handers as in right-handers. Among males, the incidence of FS+ in the CLH subgroup also was over twice that for ILH's. Thus, where left-handers report a greater incidence of FS+, and are inferior to right-handers in mental rotation skill, it is CLH's (particularly males) who contribute mostly to these effects. The results suggest that previous discrepant findings reported in studies of the cognitive correlates of left-handedness may be due in part to the mixing of two distinct left-handed subgroups. An understanding of the differences between them may be crucial for better understanding the genetic and neurobiological mechanisms underlying handedness.

Adolescent↗

Do left-handers die sooner than right-handers? Commentary on Coren and Halpern's (1991) "Left-handedness: a marker for decreased survival fitness".

Cross-sectional life span studies of handedness typically show decreasing percentages of left-handers in older age groups. In an article in Psychological Bulletin, S. Coren and D. F. Halpern (1991) argued that this age trend reflects the shorter life span of left-handers than right-handers. They presented 2 studies of their own providing what they regard to be direct evidence that left-handers, on average, die sooner than right-handers. They also proposed a variety of reasons for what they called left-handers' "decreased survival fitness." I discuss Coren and Halpern's reasons for rejecting a more conventional explanation of the life span data; the 2 studies that they offered in support of their argument; their analysis of other evidence they invoked to account for left-handers' putative decreased survival fitness; and, finally, new studies in which the longevity explanation was tested by more direct means than have been used thus far. I conclude that the case for the "decreased survival fitness" hypothesis cannot be sustained.

Adolescent↗

The impact of caring and connectedness on adolescent health and well-being.

This study of over 36,000 7th-12th grade students focused on protective factors against the quietly disturbed and acting out behaviours, which together represent the major social morbidities of adolescence. Multivariate models developed separately for girls and boys repeatedly demonstrated the protective function of caring and connectedness in the lives of youth, particularly a sense of connectedness to family and to school. A sense of spirituality, as well as low family stress (referring to poverty, unemployment, substance use and domestic violence) also functioned as protective factors. Measures of caring and connectedness surpassed demographic variables such as two parent vs single parent family structure as protective factors against high risk behaviours. Interventions for youth at-risk must critically examine the ways in which opportunities for a sense of belonging may be fostered, particularly among youth who do not report any significant caring relationships in their lives with adults.

Adolescent↗

Role of amino acids and enhancement cardioplegia in routine myocardial protection. Experimental results.

The purpose of this study was to determine the effects of the addition of amino acids to blood cardioplegic solution and the value of terminal cardioplegia enhancement techniques in routine myocardial protection. Forty-five open-chest adult dogs were instrumented with sonomicrometry crystals to measure left ventricular long axis, midequatorial short axis, and wall thickness. The aorta was clamped for 120 minutes of cardiopulmonary bypass. Animals were randomly separated into four myocardial protection groups: (1) blood cardioplegic solution with amino acids and no terminal cardioplegia (n = 12); (2) blood cardioplegic solution with amino acids and warm amino acid terminal cardioplegia (n = 11); (3) blood cardioplegic solution with amino acids and cold amino acid terminal cardioplegia (n = 12); and (4) blood cardioplegic solution plus cold terminal cardioplegia (no amino acids, n = 10). Data for preload recruitable stroke work were obtained by inflow occlusion before bypass (baseline) and at 30 and 60 minutes after reperfusion and analyzed for changes in x-intercept and slope. A significant rightward shift in x-intercept did not occur in any group. When cardiac function was expressed as a percentage of baseline preload recruitable stroke work slope, improved functional recovery was seen at both 30 and 60 minutes in groups 2 (88.6% and 91.8%), 3 (85.8% and 86.9%), and 4 (88.6% and 92.6%) compared with group 1 (77.3% and 79.2%, p < 0.05). No significant difference was found in the degree of functional recovery among groups 2, 3, and 4. These results suggest that for myocardial protection of 2 hours in nonischemic hearts, a terminal dose of blood cardioplegic solution before unclamping is beneficial, but this positive effect is independent of amino acid supplementation and temperature.

Amino Acids↗

The three-dimensional structure of an intact monoclonal antibody for canine lymphoma.

Crystal structures of Fab antibody fragments determined by X-ray diffraction characteristically feature four-domain, beta-barrel arrangements. A human antibody Fc fragment has also been found to have four beta-barrel domains. The structures of a few intact antibodies have been solved: in two myeloma proteins, the flexible hinge regions that connect the Fc to the Fab segments were deleted so the molecules were non-functional, structurally restrained, T-shaped antibodies; a third antibody, Kol, had no hinge residues missing but the Fc region was sufficiently disordered that it was not possible to relate its disposition accurately with respect to the Fab components. Here we report the structure at 3.5 A resolution of an IgG2a antitumour monoclonal antibody which contains an intact hinge region and was solved in a triclinic crystal by molecular replacement using known Fc and Fab fragments. The antibody is asymmetric, reflecting its dynamic character. There are two local, apparently independent, dyads in the molecule. One relates the heavy chains in the Fc, the other relates the constant domains of the Fabs. The variable domains are not related by this 2-fold axis because of the different Fab elbow angles of 159 degrees and 143 degrees. The Fc has assumed an asymmetric, oblique orientation with respect to loosely tethered yet almost collinear Fabs. Our study enables the two antigen-binding segments as well as the Fc portion of a functional molecule to be visualized and illustrates the flexibility of these immune response proteins.

Animals↗

Multiple valve operation for advanced valvular heart disease: results and risk factors in 513 patients.

To assess the results and incremental risk factors affecting outcome after multiple-valve operation in the early blood cardioplegia era of cardiac surgery, follow-up data (mean +/- SD 3.1 +/- 2 years) were obtained on 97% of 513 patients (mean age +/- SD 58.8 +/- 10.5 years) who underwent a multiple-valve procedure between June 1976 and August 1985. Preoperatively 41% of patients were in New York Heart Association functional class III and 54% in class IV. Three groups accounted for 98.6% of the patients: 57.7% had an aortic and mitral valve procedure, 29% had a mitral and tricuspid valve procedure and 11.9% had a triple-valve procedure. The overall hospital mortality rate was 12.5% and overall 5-year survival rate was 67.1%. Hazard function analysis for all deaths revealed systolic pulmonary artery pressure (p less than 0.0001), age (p = 0.005), triple valve procedure (p less than 0.005), concomitant coronary bypass operation (p less than 0.005) and prior cardiac surgery (p less than 0.002) as the significant incremental risk factors predicting decreased survival in the early hazard phase; diabetes (p less than 0.005) predicted decreased survival in the late hazard phase. Postoperatively the condition of 80% of the patients improved to functional class I or II; only 0.6% remained in functional class IV. The 5-year rate of freedom from late combined valve-related morbidity was 81.7% and that of freedom from late combined valve-related morbidity and mortality was 71.7%. These results demonstrate excellent clinical improvement and late survival after multiple valve operation in patients with advanced valvular heart disease, justifying aggressive surgical therapy in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Bioprosthesis↗

Subjective mood state and perception of emotion in chimeric faces.

Levy, Heller, Banich, and Burton (1983) have shown that hemispheric activational, or arousal, style, as measured by direction and consistency of choice of the "happer face" on a free-viewing Chimeric Faces Test, is highly reliable and varies across individuals who otherwise presumably have similar cortical organization (e.g., right-handed college students). The current experiment asks whether such individual differences in hemispheric arousal style are moderated by long-term, in the sense of enduring, individual differences in mood, as measured by the Profile of Mood States (POMS) questionnaire. Like Levy et al.'s subjects, most of our subjects (126 right-handed college students) made most of their choices on the Chimeric Faces Test based on the emotional cue (the smile) positioned in the half of the face to the viewer's left, or left visual hemifield (LVH), whereas a small minority were equally consistent in making their choice based on the emotional cue positioned in the half of the face to the viewer's right, or right visual hemifield (RVH). Performance on the Chimeric Faces Test, however, proved to be unrelated to scores on the POMS questionnaire. This suggests that hemispheric arousal style, as indexed by the Chimeric Faces Test, is robust enough, for a population of normal right-handers, to transcend any differences in mood as measured by the POMS questionnaire.

Adolescent↗

Characterization of two nisin-producing Lactococcus lactis subsp. lactis strains isolated from a commercial sauerkraut fermentation.

Two Lactococcus lactis subsp. lactis strains, NCK400 and LJH80, isolated from a commercial sauerkraut fermentation were shown to produce nisin. LJH80 was morphologically unstable and gave rise to two stable, nisin-producing (Nip+) derivatives, NCK318-2 and NCK318-3. NCK400 and derivatives of LJH80 exhibited identical morphological and metabolic characteristics, but could be distinguished on the basis of plasmid profiles and genomic hybridization patterns to a DNA probe specific for the iso-ISS1 element, IS946. NCK318-2 and NCK318-3 harbored two and three plasmids, respectively, which hybridized with IS946. Plasmid DNA was not detected in NCK400, and DNA from this strain failed to hybridize with IS946. Despite the absence of detectable plasmid DNA in NCK400, nisin-negative derivatives (NCK402 and NCK403) were isolated after repeated transfer in broth at 37 degrees C. Nisin-negative derivatives concurrently lost the ability to ferment sucrose and became sensitive to nisin. A 4-kbp HindIII fragment containing the structural gene for nisin (spaN), cloned from L. lactis subsp. lactis ATCC 11454, was used to probe genomic DNA of NCK318-2, NCK318-3, NCK400, and NCK402 digested with EcoRI or HindIII. The spaN probe hybridized to an 8.8-kbp EcoRI fragment and a 10-kbp HindIII fragment in the Nip+ sauerkraut isolates, but did not hybridize to the Nip- derivative, NCK402. A different hybridization pattern was observed when the same probe was used against Nip+ L. lactis subsp. lactis ATCC 11454 and ATCC 7962. These phenotypic and genetic data confirmed that unique Nip+ L. lactis subsp. lactis strains were isolated from fermenting sauerkraut.

Animals↗

Novel paired starter culture system for sauerkraut, consisting of a nisin-resistant Leuconostoc mesenteroides strain and a nisin-producing Lactococcus lactis strain.

Nisin-resistant Leuconostoc mesenteroides NCK293 and nisin-producing Lactococcus lactis subsp. lactis NCK401 were evaluated separately and in combination for growth and nisin production in a model sauerkraut fermentation. Strains were genetically marked and selectively enumerated by using antibiotic-containing media. The growth and survival of L. mesenteroides were similar in the presence and absence of Lactococcus lactis subsp. lactis. The growth of Lactococcus lactis subsp. lactis was not inhibited, although the maximum cell density was reduced and the population decline was more pronounced in the presence of L. mesenteroides. Nisin was detected within 24 h, and levels were relatively constant over the 12-day test period. The maximum cell populations and nisin level achieved could be altered by changing the initial cell ratios of L. mesenteroides and lactococcus lactis subsp. lactis. Isogenic nisin-producing and nisin-negative Lactococcus lactis subsp. lactis derivatives were used in combination with nisin-resistant L. mesenteroides to demonstrate that nisin levels produced in mixed culture were sufficient to retard the onset of the growth of nisin-sensitive, homofermentative Lactobacillus plantarum ATCC 14917.

Colony Count, Microbial↗

Effect of light chain V region duplication on IgG oligomerization and in vivo efficacy.

A human immunoglobulin G1 (IgG1) antibody oligomer was isolated from a transfected myeloma cell line that produced a monoclonal antibody to group B streptococci. Compared to the IgG1 monomer, the oligomer was significantly more effective at protecting neonatal rats from infection in vivo. The oligomer was also shown to cross the placenta and to be stable in neonatal rats. Immunochemical analysis and complementary DNA sequencing showed that the transfected cell line produced two distinct kappa light chains: a normal light chain (Ln) with a molecular mass of 25 kilodaltons and a 37-kilodalton species (L37), the domain composition of which was variable-variable-constant (V-V-C). Cotransfection of vectors encoding the heavy chain and L37 resulted in production of oligomeric IgG.

Animals↗